Most diseases do not result from a single etiology, but rather from multiple interacting events involving numerous bodily systems and producing a constellation of symptoms and chronic impairment for the suffering patients. One such complex, chronic medical disorder has manifested in veterans of armed conflict in the Middle East during the 1990's.
An alarming number of Gulf War veterans returning from Operation Desert Storm have been afflicted with a complex constellation of symptoms including debilitating fatigue, musculoskeletal discomfort, skin rashes, and cognitive dysfunction (Haley R. W. Am J Epidemiol 146(9):695-703 1997; Fukuda K. et al. JAMA 280:981-998 1998; Wolfe J. et al. Am J Ind Med 33(2):104-113 1998). There is still no clear understanding of Gulf War Syndrome (GWS), also called Gulf War Illness (GWI), although evidence is mounting of immunological dysfunction in this population that may be potentiated by response to stress whether physiological, psychological, chemical, or other. Indeed clinical presentation of GWI overlaps strongly with that of another stress-mediated complex, chronic medical disorder: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), also called Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) (Kang H. et al. Am J Epidemiol 157:141-148 2003; Elsen S. et al. Ann Int Med 142:881-890 2005). Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been linked to the pathophysiology of both GWI (Golier J. et al. Psychoneuroendocrinology 31(10):1181-1189 2006; Golier J. et al. Biol Psychiatry 62(10):1175-1178 2007; Unwin C. et al. Lancet 353:169-178 1999) and ME/CFS (Crofford L. et al. Brain Behav Immun 18:314-325 2004). Associated pathophysiology includes hypersensitivity of normal cytokine feedback to the HPA axis (Johnson J. et al. Neuroscience 127(3):569-577 2004) as well as the expected stress-induced release of neuropeptides such as neuropeptide-Y (NPY) and its mediation of innate immune response and cortisol levels (Morgan C. et al. Biol Psychiatry 52(2):136-142 2002).
Changes within the immune signaling network have also been observed in GWI and ME/CFS. There is a growing body of evidence supporting a significant role for factors produced by the nervous and endocrine systems in altering immune cell function (Butts C. et al. Cell Immunol 252(1-2):7-15 2008).
Without being bound by theory, it is proposed that complex, chronic medical disorders such as GWI and ME/CFS present with distinct patterns of immune signaling which will be different from the healthy, normal patterns. Considering the extensive amount of debilitating symptoms experienced by persons suffering from these conditions, it would be very advantageous to develop methods for analyzing and comparing these immune signaling patterns for identification of potential therapeutic targets and development of improved treatment strategies.